What is the difference between dapagliflozin (SGLT2 inhibitor) and empagliflozin (SGLT2 inhibitor) in treating type 2 diabetes?

Dapagliflozin vs Empagliflozin: Clinical Equivalence

Both dapagliflozin and empagliflozin demonstrate equivalent cardiovascular and renal benefits in patients with type 2 diabetes, and the choice between them should be based on practical considerations such as cost, availability, and dosing convenience rather than efficacy differences. 1, 2

Evidence for Clinical Equivalence

Cardiovascular Outcomes

• No significant difference exists between empagliflozin and dapagliflozin for major adverse cardiovascular events (MACE) in the largest head-to-head comparison involving over 57,000 patients with type 2 diabetes 1
• The 6-year adjusted absolute risk of MACE was identical: 10.0% for both agents (risk ratio 1.00,95% CI 0.91-1.11) 1
• A Scandinavian cohort study of nearly 200,000 patients confirmed similar risks for myocardial infarction (HR 1.00), stroke (HR 1.03), and cardiovascular death (HR 1.01) 2
• Meta-analysis found no significant differences in myocardial infarction (RR 0.81,95% CI 0.60-1.09), heart failure (RR 0.76,95% CI 0.56-1.04), or cardiovascular mortality (RR 0.46,95% CI 0.18-1.20) 3

Heart Failure Outcomes

• Both agents reduce heart failure hospitalization by approximately 27-35% compared to placebo in their respective trials 4
• Direct comparison shows equivalent heart failure outcomes: 6.5 vs 6.3 events per 1000 person-years (HR 1.05,95% CI 0.97-1.14) 2
• This equivalence holds true regardless of baseline heart failure status 1

Renal Outcomes

• Both agents demonstrate similar renoprotective effects with no significant difference in serious renal events: 3.7 vs 4.1 events per 1000 person-years (HR 0.97,95% CI 0.87-1.07) 2
• Both reduce progression of chronic kidney disease and are recommended for patients with diabetic kidney disease 4
• Empagliflozin showed slightly lower risk for renal replacement therapy (HR 0.77,95% CI 0.60-0.99), though this did not translate to overall renal outcome differences 2

Guideline Recommendations

Class Effect Recognition

• The American Diabetes Association recognizes empagliflozin, canagliflozin, and dapagliflozin as having demonstrated cardiovascular benefit, with lesser benefits seen with ertugliflozin 4
• SGLT2 inhibitors are recommended as a class for patients with type 2 diabetes and established ASCVD, multiple risk factors, or chronic kidney disease 4
• Meta-analyses confirm SGLT2 inhibitors reduce atherosclerotic MACE to a comparable degree across the class 4

Specific Indications

Both agents share FDA approval for:

• Improving glycemic control in type 2 diabetes 4, 5, 6
• Reducing cardiovascular death in patients with established cardiovascular disease 4
• Reducing heart failure hospitalization 4, 5

Dapagliflozin has additional FDA approval for:

• Reducing cardiovascular death and heart failure hospitalization in adults with heart failure with reduced ejection fraction, regardless of diabetes status 4, 5

Practical Considerations

Dosing

• Dapagliflozin: 10 mg once daily 4, 5
• Empagliflozin: 10 mg once daily 4
• Both require dose adjustment or discontinuation when eGFR falls below specific thresholds 4

Renal Dosing Differences

• Empagliflozin: not recommended for glycemic control when eGFR <45 mL/min/1.73 m² 4
• Dapagliflozin: not recommended for glycemic control when eGFR <45 mL/min/1.73 m²; contraindicated when eGFR <30 mL/min/1.73 m² 4

Safety Profile

• Both agents share similar adverse effect profiles including genital mycotic infections, urinary tract infections, and risk of euglycemic diabetic ketoacidosis 4, 5, 6
• Discontinue both agents at least 3 days before planned surgery to prevent postoperative ketoacidosis 4, 5
• No significant difference in diabetic ketoacidosis risk between the two agents (HR 1.12,95% CI 0.94-1.33) 2

Clinical Decision Algorithm

For patients with type 2 diabetes requiring SGLT2 inhibitor therapy:

1. If patient has heart failure with reduced ejection fraction without diabetes: Choose dapagliflozin (has specific FDA indication for this population) 4, 5

2. If patient has type 2 diabetes with established ASCVD, multiple risk factors, or CKD: Either agent is appropriate; select based on formulary coverage, cost, or patient/provider preference 4, 1, 2

3. If patient has type 2 diabetes without established cardiovascular disease or CKD: Both agents reduce ASCVD, heart failure, and renal events equivalently 7

4. If cost is a primary concern: Choose the agent with better insurance coverage or lower out-of-pocket cost, as clinical outcomes are equivalent 1, 2

Key Clinical Pearls

• The cardiovascular and renal benefits of both agents appear independent of glucose-lowering effects, as benefits are seen across HbA1c ranges 4, 5
• Treatment decisions should be made independently of baseline HbA1c or individualized HbA1c target in high-risk patients 4
• Both agents can be combined with GLP-1 receptor agonists for complementary cardiovascular and renal benefits 6
• The class effect is robust across subgroups including those with and without atherosclerotic cardiovascular disease or heart failure 1, 7